Broadly reactive antitumor cytotoxic cell responses, generated in vitro by mouse splenocytes cultured with the lymphokine IL2, are modulated in a strain-dependent fashion by addition of polyinosinic acid (Poly I) to the cultures. Although Poly I is a synthetic polynucleotide, macromolecular polyanionic carbohydrates, some of which occur naturally in man, have been identified which act like Poly I. Studies of mouse strains whose splenocytes generate only low levels of antitumor cytotoxicity with Poly I, show that suppressive cell-cell interactions contribute to the low responses.